Polymorphism in nimodipine raw materials: Development and validation of a quantitative method through differential scanning calorimetry

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 70; pp. 188 - 193
• Main Authors: Riekes, Manoela Klüppel, Pereira, Rafael Nicolay, Rauber, Gabriela Schneider, Cuffini, Silvia Lucia, Campos, Carlos Eduardo Maduro de, Silva, Marcos Antonio Segatto, Stulzer, Hellen Karine
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-11-2012; Elsevier
• Subjects: Analysis; Analysis of Variance; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calcium Channel Blockers - chemistry; Calibration; Calorimetry, Differential Scanning - standards; Crystallization; Crystallography, X-Ray; Differential scanning calorimetry; Fundamental and applied biological sciences. Psychology; General pharmacology; Limit of Detection; Linear Models; Medical sciences; monitoring; Nimodipine; Nimodipine - chemistry; Pharmacology. Drug treatments; Polymorphism; Powder Diffraction; Raman spectroscopy; raw materials; Reproducibility of Results; Spectrum Analysis, Raman; X-radiation; X-ray powder diffraction; Differential scanning calorimetry; Nimodipine; X-ray powder diffraction; Polymorphism; Validation; Calcium antagonist; Raw materials; Neuroprotective agent; X ray diffraction; Powder; Development; Dihydropyridine derivatives; Differential method; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2012.06.029

► A DSC-validated method was developed in order to evaluate the polymorphic content in nimodipine raw materials. ► The method was considered linear, specific, accurate, robust and precise. ► Nimodipine raw materials revealed a polymorphic mixture content.
Due to the physical–chemical and therapeutic impacts of polymorphism, its monitoring in raw materials is necessary. The purpose of this study was to develop and validate a quantitative method to determine the polymorphic content of nimodipine (NMP) raw materials based on differential scanning calorimetry (DSC). The polymorphs required for the development of the method were characterized through DSC, X-ray powder diffraction (XRPD) and Raman spectroscopy and their polymorphic identity was confirmed. The developed method was found to be linear, robust, precise, accurate and specific. Three different samples obtained from distinct suppliers (NMP 1, NMP 2 and NMP 3) were firstly characterized through XRPD and DSC as polymorphic mixtures. The determination of their polymorphic identity revealed that all samples presented the Modification I (Mod I) or metastable form in greatest proportion. Since the commercial polymorph is Mod I, the polymorphic characteristic of the samples analyzed needs to be investigated. Thus, the proposed method provides a useful tool for the monitoring of the polymorphic content of NMP raw materials.